Ibuprofen is a widely used nonsteroidal antiinflammatory drug. It inhibits prostaglandin synthesis and thus has the potential to inhibit carcinogenesis. Ibuprofen has been selected by the Chemoprevention Decision Point Committee of the Division of Cancer Prevention and Control from among over 500 agents as having high priority for further consideration as a potential cancer chemoprenventive agent, particularly for cancers of the bladder, breast, and lung. The decisions of the Committee of necessity, were based almost entirely on animal and in vitro data. Data on human populations are desirable before the initiation of clinical trials. We propose to assess the potential protective effect of ibuprofen use against cancers, including bladder, breast, and lung, using data collected from 60,000 patients in a multiple case-control study devoted to the evaluation of medication use in relation to the incidence of serious illness, particularly cancers. Standard interviews were used to obtain information on lifetime history of regular medication use, demographic factors, habits (e.g., cigarette smoking), medical history, and other factors. Ibuprofen use was reported by 3.3% of the men and 6.0% of the women, and 40% to 50% of the users had total durations of use of at least one year. Data are available on 200 newly diagnosed patients with bladder cancer, 4300 with breast cancer, and 1350 with lung cancer. The cancers will be assessed in relation to ibuprofen use before the occurrence of the illness, with use classified according to duration and recency. The case groups will be compared with appropriate controls selected from among patients who do not have the cancers of interest and who have conditions unrelated to the use of ibuprofen. The potential confounding effects of other factors (e.g., smoking for lung cancer) will be controlled using multiple logistic regression. It will be possible to assess other nonsteroidal antiinflammatory drugs as well (e.g., indomethacin) and also other cancer sites (e.g., colon, 940 patients; rectum, 650 patients). Our data base provides the opportunity to assess, at minimal cost, the potential protective effect of ibuprofen against several cancers. The value of the data has already been amply demonstrated, e.g., in establishing the inverse associations of ovarian and endometrial cancers with oral contraceptive use.